乳腺癌中的脂联素受体1表达及其信号通路激活对癌细胞的作用机制研究  

Expression of Adiponectin R1 and its Signaling Pathway In Breast Cancer

作　　者：鲍轶[1] 钟征翔[1] 崔戈[1] 

机构地区：[1]浙江省嘉兴市第二医院,314000

出　　处：《医学研究杂志》2012年第10期38-41,共4页Journal of Medical Research

基　　金：国家自然青年科学基金资助项目(81101707);浙江省中医药基金资助项目(2011ZA104)

摘　　要：目的探讨人能量代谢相关基因脂联素受体1(AdipoR1)在乳腺癌中的表达及其信号通路激活对乳腺癌细胞的作用机制。方法采用已发表的基因表达数据库数据,分析AdipoR1在各病理亚型中的不同表达,以及AdipoR1基因表达与HER-2表达的相关性。采用免疫印迹法(Western blotting)检测AdipoR1在MCF-7、MDA-MB-231和SKBR3等ER+、HER-2+及ER-癌细胞株中的表达;采用Western blotting法检测MCF-7细胞在脂联素不同时间长度的作用下,细胞内信号蛋白AMPK及S6激酶(S6K)的活化。结果 AdipoR1在正常乳腺组织样乳癌中基因表达最低,与其他各组病理亚型乳癌有显著性差异(P<0.05)。在乳腺癌中,AdipoR1基因表达与HER-2基因呈正相关(Pearson,r=0.134)。AdipoR1广泛表达于ER+、HER-2+及ER-乳腺癌细胞系中。在低浓度(0.5μg/ml)脂联素作用下,AMPK及mTOR的底物蛋白S6K在15min发生磷酸化活化,磷酸化信号随着时间延长而加强,30min时信号强度达到最高峰;之后开始下降,但在1h仍能检测到磷酸化。结论 AdipoR1基因表达水平在各乳腺癌病理亚型不同,该受体在各类乳腺癌细胞株中广泛表达。乳腺癌中的脂联素信号通路激活,可活化AMPK及mTOR信号通路,从而影响肿瘤细胞的能量代谢、蛋白合成及细胞增殖过程。Objective To investigate the energy metabolism- related gene adiponectin receptor 1 （AdipoR1） in breast cancer and the effects of its signaling pathway activation on breast cancer ceils. Methods Using the published gene expression data set in database, the different gene expression of AdipoR1 were analyzed in various subtypes of breast cancer, and AdipoRl gene expression is positively correlated with and HER -2 expression. Western blotting was used to examine the AdipoR1 protein expression in ER ~ , HER -2 ~ and ER- cell lines, including MCF -7, MDA -MB -231 and SKBR3. After MCF -7 cells were exposed in the media with recombinant adi- ponectin in varieties of time points, the activity of AMPK kinase and $6 kinase were also examined. Results The gene expression of Adi- poR1 was significantly low in normal breast - like breast cancer comparing with other pathological subtypes （ P 〈 0.05 ）. AdipoRl gene ex- pression was positively correlated with HER -2 gene in breast cancer （Pearson r = 0. 134）. AdipoR1 was widely expressed in ER ＋ , HER -2 ＋ and ER- breast cancer cell lines. In addition, the administration of 0.5t^g/ml of adiponectin to MCF -7 cells, AMPK and $6 ki- nase were rapidly phosphorylated in 15min and further increased in 30min, but declined in lb. Conclusion There was difference in the mRNA level of AdipoR1 in a varieties of subtypes of breast tumor tissue, and widely expressed both in ER ＋ , HER - 2 ＋ and ER - breast cancer. In tumor cells, the activation of adiponectin and its receptor signaling pathway could influence energy metabolism, protein synthe- sis and cell proliferation through activation of AMPK and roTOR pathway.

关 键 词：乳腺癌 脂联素受体1 基因表达 腺苷酸活化蛋白激酶 S6激酶 

分 类 号：R73-361[医药卫生—肿瘤]